Sizwe’s* Maths teacher couldn’t — and therefore didn’t — teach his class the full Matric syllabus because, the bright young learner realised, she didn’t fully grasp some of the concepts herself.

But he drove himself through hours of studying by paraffin lamp and came out as the top Matric student in his Gauteng township school. He got a bursary and went to university, battling with the transition and a world of students who had been to better schools and wore better clothes and thought someone who didn’t have a “Model C accent” was not worth befriending.

Sizwe got his articles at the first go-round, leaving in his dust many of the snooty students in his class.
Today, he lives in a cluster home in Midrand, drives an Audi, holds down a management position in a large corporate and has a loving wife who is as successful as he.

Society says he should be happy. Instead, a slow burn of inexplicable anger, an inability to sleep at night, a loss of interest in sex and a bleak, grey mood drove him to a psychologist, who diagnosed depression.

“This is a phenomenon that’s especially prevalent in contemporary South Africa,” says clinical psychologist Zamo Mbele, who is working on an article for publication on the topic. “A lot of upwardly mobile young black South Africans come from a background that is less than successful or even seriously disadvantaged. They get caught between two worlds: their present world with its potential for wealth, and a previous world with a history of sheer poverty, or even just lower middle class circumstances very different to where they are now.

“This causes a lot of bewilderment. The possibility of — or realisation of — achievement and wealth contrasts with the circumstances of family and friends and causes a lot of anxiety.”

Been there, got the T-shirt

A whole generation of younger South Africans is forging its way through this transitional experience, but it is not unique to our country. In Bluestockings: The Remarkable Story of the First Women to Fight for an Education (Penguin 2010), Jane Robinson recounts the stories of British women who pioneered higher education for women in an era when scientists genuinely debated whether women’s brains were too small to cope with knowledge and a woman was not able to draw money from a bank account without “a responsible male” in attendance.

Many of the girls who secured places at universities from Liverpool to Cambridge thanks to scholarships provided by progressive benefactors were disadvantaged by being female and came from poor families.

“The fresher’s first homecoming after being away for a term could be awkward. Family dynamics had altered and expectations changed. There might be jealously and resentment from siblings forced to make sacrifices, or suspicion from parents unsure what their daughters had become,” Robinson writes.

One girl wrote in her diary: “Life is poisoned at the very root. I’m being educated out of my real class in society and made unnaturally critical of my own parents.”

In a huge body of literature and research, the children of immigrants to countries like the US tell of a similar experience, in painful words that speak of the tearing relationships, the shifting identities and the emotional toll of such a massive change.

Many clinicians, including Mbele, refer to the phenomenon as “survivor guilt”. (The term is more usually associated with people who have survived a great disaster — such as a tsunami - in which others died.)

In this instance, survivor guilt affects people who have managed to escape dreadful circumstances —such as deep poverty — but have left family, school friends and playmates behind. And survivor guilt often results in conditions such as anxiety disorders or depression.

Alone on the edge of the world

The young South Africans who are in the vanguard of this phenomenon are usually unaware that others before them have experienced anything like this, or that therapy might be necessary, says Mbele.

“There’s no template for this. And it’s counter-intuitive — why would you be miserable when you’re achieving the dreams of your parents? So they don’t easily seek help.”

With no precedent in their experience, Mbele says they feel very alone. The requirement to deal with identity disparities takes its toll.

“They have to negotiate themselves into the position of being a ‘have’ from being a ‘have-not’. They suffer a sense of dispossession; they don’t quite belong in the township anymore, but similarly, they don’t quite belong among the people they’re surrounded by, who have always had privilege.”

Negotiating their way through this new landscape can mean being permanently on edge: they don’t always know how to behave, from simple things like not knowing what cutlery to use at very formal occasions (many of those British women-students would recognise that problem) to complex things like not having the social keys to unlock the behaviour of colleagues or superiors that everyone else in a meeting is able to decode without difficulty.

It wreaks havoc with families too, Mbele says. “Parents are very excited to see their children succeed. But then they experience a loss because of how far [their children] moved away [both physically and socially]. It might be accompanied by feelings of envy and even of rage.”

But why do some people end up deep in a trough of clinical depression, while others do not? And what exactly is clinical depression, and how does it differ from a state of “low mood”, a simple sadness that some people feel when they go home for Christmas and experience the gulf between them and their families?

Biological burden

There’s a persistent myth that being sad is not good. We’ve developed a tendency to equate sadness with depression and use the term casually in this context.

“Feelings of sadness,” Johannes-burg psychiatrist Dr Theona Ballyram says, “are a normal part of the spectrum of emotion.”

For instance, it is perfectly normal to suffer feelings of intense sadness and prolonged low mood after a bereavement, or to react to a divorce or job-loss with a bout of feeling blue.

Dr Ronald Pies wrote on PsychCentral last year: “The normally grieving person typically maintains the hope that things will get better. In contrast, the clinically depressed person’s mood is almost uniformly one of gloom, despair, and hopelessness — nearly all day, nearly every day.

“And, unlike the typical bereaved person, the individual with major depression is usually quite impaired in terms of daily functioning. “Furthermore, in ordinary grief, the person’s self-esteem usually remains intact. In major depression, feelings of worthlessness and self-loathing are very common.”

When these feelings — and a range of other symptoms, such as loss of interest in sex and other activities, altered sleep patterns and changes in eating habits — persist for two weeks or more, a psychiatrist will usually diagnose clinical depression.

Ballyram says clinical depression is a condition that “we still don’t fully understand”. It has “a strong biological component”, which has given rise to a range of hypotheses about what causes it.

They include dysregulation of neurotransmitters (such as serotonin, the focus of much drug therapy for depression), abnormalities in the circadian rhythm (the biological clock), inflammation, or decreased levels of the protective protein called brain-derived neurotrophic factor.

It is clear that clinical depression is multifactorial, says Ballyram, in that it involves the interaction of the genes and the environment. “Depression runs in families, but we don’t understand the exact nature of the heritability,” she says. “It’s not strictly Mendelian.”

In other words, depression is not related to one dominant or recessive gene, but rather involves a number of potential genes, only some of which have as yet been identified. “And you may have a strong depressive suite of genes but never manifest with depression, if you have good protective factors,” she says.

Protective factors would include things like a stable family, good support systems, high levels of education, a lack of substance abuse and good eating and exercise habits. On the other hand, people who have no detectable genetic susceptibility for depression could, under a tidal wave of life events, succumb.

Remaking DNA

Enter “behavioural epigenetics”, a startling new field which is only about 20 years old. “Epigenetics” is, broadly, the study of heritable genetic changes — such as changes to the proteins (histones) around which DNA is wrapped and DNA mythelation (the addition of a methyl group to the DNA) — that are not caused by changes in the sequence of the DNA.

Think of a jersey (the genetic material you were born with) that has been washed over and over again (life experiences), and has changed over the years. It still has the same amount of stitches in each row (the DNA sequence is unchanged), but some stitches have stretched a bit (DNA methylation), and others have gained little fluffballs (changes to the histones). It is still very much a jersey, but it has changed in small ways.

“Behavioural epigenetics” studies the role of epigenetics in shaping animal (including human) behaviour. (You wouldn’t wear the jersey mentioned above to a formal dinner, but you’d be quite happy snuggling up in it on a winter evening.)

As Discovery magazine put it in its May 2013 edition: “The genome has long been known as the blueprint of life, but the epigenome is life’s Etch A Sketch.”

A mother who lived through the recent wars in Sierra Leone, people who suffered abandonment as children and children who survived abuse, could all have had epigenetic changes that make not only them more vulnerable to depression, but also, since these changes can be handed down through the generations, their children and grandchildren.

Luckily, positive experiences can alter the epigenome for the better. A person who hails from a loving family in a poor but stable community may find the transition to a vastly different life challenging, but could conceivably find a path without succumbing to clinical depression. A different person, with different genes and epigenetics, would be biologically disposed to fall into a deep, dark state which is very hard to escape without help from professionals and understanding from family and friends.

A new road to follow?

The inflammation model of depression is, says Ballyram, “a very exciting new hypothesis which opens the possibility of new treatment modalities”. It adds weight to the concept of depression as a biological condition, too.

We’ve long known that depression was associated with a wide range of physical illnesses — such as heart disease, diabetes and cancer, all diseases that provoke an inflammatory response. The inflammation hypothesis provides a possible biological mechanism for this link.

Major depression is common in the context of autoimmune diseases, too, “and is frequently associated with persistently raised levels of proinflammatory cytokines and other markers of inflammation, even in the absence of another diagnosable immune pathology to account for these findings”, according to a study published in the May 2012 edition of the scientific journal Drug Discovery Today.

In other words, even physically healthy people with depression often have inflammation. Writing an opinion piece with colleagues in the journal BMC Medicine last year, Professor Michael Berk of Deakin University’s School of Medicine, said: “There is now an extensive body of data showing that depression is associated with both a chronic low-grade inflammatory response, activation of cell-mediated immunity and activation of the compensatory anti-inflammatory reflex system.”

This ties in with research by many other scientists that links depression and dysfunctional gut bacteria, which is associated with chronic inflammation as well. (And let’s not forget the immense role the gut plays in the nervous system — it’s often called “the second brain” and has more neurons than the spinal cord.)

Inflammation also could explain links between depression and environmental factors such as air pollution. Dr Yun-Chul Hong of Seoul National University and his colleagues found a strong link between depression in elderly people and particulate matter in the air. He writes: “Regarding the mechanism, I agree with the idea that air pollution gives rise to inflammation in the brain. Probably air pollutants cause oxidative stress in the brain and the oxidative stress leads to inflammation reaction. Another mechanism would be mitochondrial dysfunction which is also associated with oxidative stress. It may reduce dopaminergic activity, so depression occurs.” (Dopamine is a neurotransmitter and related to reward-motivated behaviour.)

Many factors in contemporary urban life are known to trigger inflammation, from chronic low-grade stress to poor diets. Stress is a top trigger of inflammation. Last year, researchers at Ohio State University found that even thinking about previous stressful events raises markers of inflammation in the blood — and as Mbele notes, South Africans have a bucket-load of stress to deal with, from crime to traffic jams. If and when this hypothesis proves out, a whole new world of possible treatment will open up for medical professionals.

Either way, depression, like many other mental illnesses, does not necessarily limit someone’s ability to be productive and contribute to society. From Charles Dickens to Agatha Christie, from Winston Churchill to Louis CK, from Hugh Laurie to Mozart, many highly talented people have suffered one or more episodes of depression in their lives.

Bipolar disorder

Most of us seem to know at least one person who is “bipolar”, the condition that used to be known as “manic-depressive”, and which is characterised by high-energy, often abnormally happy or irritated episodes interspersed with times of deep depression.

In fact, bipolar disorder (which is a spectrum of conditions called Bipolar I, Bipolar II and Bipolar NOS) is not that common, says Johannesburg psychiatrist Dr Theona Ballyram.

“The bipolar spectrum affects 4.4% of the population,” she says. “The reason it seems so common is because the term is often used very loosely and also because it is fairly easy to misdiagnose, as a number of conditions can mimic bipolar, including substance abuse, anxiety, depression and even some medical conditions.”

The disorder has some elements in common with depression, but different genes have been identified as playing a role in the development of bipolar disorder. Like depression, it is an illness we don’t yet fully understand.

*Name changed to protect patient confidentiality.

This feature has been made possible by the financial sponsorship of Momentum Health. Contents and pictures were sourced independently by the M&G supplements editorial team.